What is the role of ketamine (anesthesia medication) drip in managing seizures?

Ketamine for Seizure Management

Ketamine is not a first- or second-line agent for seizure management but has an emerging role as a third-line option for refractory status epilepticus, particularly when traditional agents fail and intubation may be avoidable. 1, 2

Standard Treatment Algorithm for Seizures

First-Line Treatment

• Benzodiazepines remain the definitive first-line therapy for active seizures lasting ≥5 minutes or status epilepticus 1, 2
• IV lorazepam 4 mg at 2 mg/min demonstrates 65% efficacy in terminating seizures 1
• Rectal diazepam is an alternative when IV access is unavailable 1

Second-Line Treatment

After adequate benzodiazepine dosing fails, administer one of the following 1:

• Valproate 20-30 mg/kg IV over 5-20 minutes (88% seizure control, minimal hypotension risk) 1
• Fosphenytoin 20 mg PE/kg IV at maximum 150 PE/min (84% seizure control, 12% hypotension risk) 1
• Levetiracetam 30 mg/kg IV at 5 mg/kg/min (73% seizure control in refractory cases) 3, 1

Third-Line Treatment for Refractory Status Epilepticus

When benzodiazepines and second-line agents fail 1:

• Midazolam infusion is the preferred first choice: loading dose 0.15-0.20 mg/kg IV, continuous infusion 1 mg/kg/min titrated up to 5 mg/kg/min 1
• Propofol for intubated patients: 2 mg/kg bolus, continuous infusion 3-7 mg/kg/hour titrated to EEG burst suppression 1

Ketamine's Role in Seizure Management

When to Consider Ketamine

Ketamine should be considered as a third- or fourth-line agent when traditional therapies fail, particularly in scenarios where avoiding intubation is desirable. 4, 5, 6

The strongest recent evidence comes from a 2024 case series showing that ketamine without intubation achieved seizure resolution in 71.4% of patients with refractory seizures, with responders 80% more likely to have received ketamine ≥5 hours earlier than nonresponders 6. This suggests early ketamine use within the refractory phase may improve outcomes 6.

Mechanism and Rationale

• Ketamine acts as an NMDA receptor antagonist, targeting a different pathway than GABA-ergic agents (benzodiazepines, propofol) 3, 5
• In status epilepticus, NMDA receptors become upregulated while GABA receptors are downregulated, making ketamine theoretically advantageous in refractory cases 4, 5
• Unlike other continuous infusion anesthetics, ketamine does not suppress respiratory drive, potentially avoiding intubation 6

Dosing Protocols

For refractory seizures without intubation 6:

• Initial bolus: 0.9-1 mg/kg IV
• Continuous infusion: Start at 10 μg/kg/min
• Titrate to maximum 30 μg/kg/min as needed
• Median effective duration: 39.8 hours

For status epilepticus requiring intubation 4:

• 1 mg/kg IV bolus can be used as induction agent
• Consider higher anesthetic doses for deep sedation if needed 3

Critical Safety Considerations

Hemodynamic monitoring is essential 6:

• Hypotension (SBP <90 mmHg) occurred in 31.8% of patients receiving ketamine alone 6
• Hypertension (SBP >180 mmHg) occurred in 39.3% 6
• Ketamine has sympathomimetic effects that can cause dose-dependent increases in heart rate, blood pressure, and cardiac output 3, 7

Important contraindications and precautions 7, 8:

• Avoid in patients with uncontrolled cardiovascular disease, severe cardiac disease, or ischemic heart disease 7
• Emergence reactions occur in 10-30% of adults (floating sensations, vivid dreams, hallucinations, delirium) 7
• Co-administration with benzodiazepines minimizes emergence reactions 7
• Contraindicated in pregnancy 7, 8

Drug interactions 8:

• Theophylline or aminophylline may lower seizure threshold when combined with ketamine—consider alternatives 8
• Concomitant benzodiazepines or opioids may cause profound sedation and respiratory depression—monitor closely 8

Common Pitfalls to Avoid

• Never use ketamine as first-line therapy—benzodiazepines remain the standard 1, 2
• Do not skip second-line agents (valproate, levetiracetam, fosphenytoin) before considering ketamine 1
• Earlier initiation within the refractory phase appears more effective than delayed use 6
• Continuous vital sign monitoring is mandatory, particularly respiratory status and blood pressure 1, 6
• EEG monitoring should guide titration in refractory status epilepticus 1
• Prepare for respiratory support despite ketamine's favorable respiratory profile 1

Evidence Quality and Limitations

The guideline evidence for ketamine in seizures is limited. The European Heart Journal (2023) discusses ketamine primarily for post-cardiac arrest sedation, noting it has "antiseizure effects" but recommending benzodiazepines specifically for controlling active seizures 3. The Annals of Emergency Medicine guidelines (2014) focus on valproate, levetiracetam, and phenytoin for status epilepticus without mentioning ketamine 3.

The strongest evidence comes from recent research studies 4, 6, not guidelines, suggesting ketamine's role is still evolving. A 2022 case report demonstrated seizure resolution after ketamine in a 9-month-old with refractory status epilepticus who had failed multiple standard agents 4. The 2024 case series provides the most robust data showing 71.4% response rates without intubation 6.

Clinical Bottom Line

Ketamine represents a reasonable third- or fourth-line option for refractory status epilepticus, particularly when avoiding intubation is desirable, but should never replace standard benzodiazepine and second-line antiepileptic therapy. 1, 4, 6 Its unique NMDA antagonism, respiratory-sparing profile, and emerging evidence support its use in carefully selected patients with appropriate hemodynamic monitoring 5, 6.